Human low density lipoproteins (LDL) exist in either a monodisperse or polydisperse state. Polydisperse LDL is most commonly found in association with hypertriglyceridemia and diabetes mellitus. Physical studies on polydisperse LDL reveal a family of discrete lipoproteins within the LDL class which differ in molecular size. Metabolic studies now completed suggest that these lipoproteins are formed by two separate pathways, from VLDL and by de novo synthesis. The polydisperse LDL are catabolized in a sequential fashion in accord with their molecular size. The objectives of this, for the forthcoming year, are: 1) To continue our kinetic studies of polydisperse LDL utilizing 3H-leucine as a tracer and analyzing the data by computerized modeling; 2) To investigate the structural organization of these lipoproteins by physical techniques, by chemical crosslinking of apoproteins, and by studying apoprotein exchange; 3) To explore the biological import of structural differences in LDL utilizing tissue cultures of human lymphocytes to determine whether the cellular LDL receptor recognizes structural differences in LDL. BIBLIOGRAPHIC REFERENCES: Grow, T.E. and Fried, M. "Lipoprotein Geometry II. Apoprotein Exchange in Human Plasma High Density Lipoportein." Biochem. Biophys. Res. Comm. 75:117, 1977. Grow, T.E. and Fried, M. "Apoprotein Exchange Between HDL2 and HDL3, Two Subclasses of Human Plasma High Density Lipoprotein." Fed. Proc. 36:935, 1977.